Coating formulations for scoring or cutting balloon catheters

ABSTRACT

The present invention is related to scoring or cutting balloon catheters carrying at least on a portion of their surface at least one drug or drug preparation and at least one lipophilic antioxidant at a ratio of 3-100% by weight of the at least one lipophilic antioxidant in relation to 100% by weight of the drug, wherein a combination of the at least one drug being a limus drug and the at least one lipophilic antioxidant being butylated hydroxytoluene is excluded.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.13/628,627, filed Sep. 27, 2012, which is a continuation of PCTApplication No. PCT/EP2011/056179, filed Apr. 18, 2011, which claims thebenefit of EP Application No. 10160347.0, filed Apr. 19, 2010, the fulldisclosures of which are incorporated herein by reference in theirentirety.

BACKGROUND

1. Field of the Invention

The invention relates to the transfer of a drug loosely adhering to thesurface of a scoring or cutting balloon catheter to a site inside thebody, usually in a diseased blood vessel. The preferred application islocal drug therapy during percutaneous transluminal angioplasty (PTA) orpercutaneous transluminal coronary angioplasty (PTCA). The interventionsare performed to restore blood flow in stenotic or occluded bloodvessels, usually into arteries. A catheter is introduced in a majorartery. At the distal end the catheter carries a cylindrical balloon infolded state with very small diameter and additional tools or structureswhich scratch or cut the luminal surface of the treated blood vessel ortissue. In the folded state the balloon can enter or pass the stenoticor occluded segment of e.g. a blood vessel. Once positioned in thenarrowed segment, the balloon is inflated to enlarge the lumen of theblood vessel to its original diameter. Simultaneously, a drug may betransferred to the vessel wall to prevent early and late re-narrowingdue to hyperproliferation of the injured vessel wall.

Medical devices may contain drugs either to improve the tolerance,efficacy or in vivo lifetime of the device or the device serves ascarrier for the drug. In any case the dose density (e.g. mg drug/mgdevice or mg drug/mm² device surface), chemical stability, adherence,release rate, and total amount released are important and frequentlycritical features of the drug formulation. These properties are the morecritical the more the requirements during production and application ofthe device vary or may even be contradictory. Drug-coated angioplastycatheters are typical examples: the drug coating must adhere firmly totolerate mechanical stress during production including folding ofballoons, crimping of stents, packaging, transportation to customers,and during final application, which involves the passage through anarrow hemostatic valve, an introductory sheath or guiding catheter anda variable distance through possibly tortuous and narrow blood vessels.When the balloon is inflated the drug should be released within a minuteor less as rapidly and as completely as possible. The problem wasdemonstrated by Cremers et al. (Cremers B, Biedermann M, Mahnkopf D,Bohm M, Scheller B. Comparison of two different paclitaxel-coatedballoon catheters in the porcine coronary restenosis model. Clin ResCardiol 2009; 98:325-330) who retrieved as much as 50% of the dose fromballoons after expansion for one minute in coronary arteries of pigs,whereas other catheters coated with the same drug and dose but in adifferent formulation released more than 95%. Almost perfect results(i.e., loss of only 10% of dose and residual drug on the balloon afterexpansion in an artery of about 10%) were achieved with a rigidprototype balloon (Scheller B, Speck U, Abramjuk C, Bernhardt U, Bohm M,Nickenig G. Paclitaxel balloon coating—a novel method for prevention andtherapy of restenosis. Circulation 2004; 110: 810-814). The applicationof the same coating composition to more flexible modern ballooncatheters resulted in problems, i.e., larger premature loss of the drug.The coating of scoring or cutting balloons with drugs in a reliable waywith a dose which sufficient to be efficacious imposes additionalproblems because of the more complex structure of the device and themore complex production process.

2. Prior Art

Protection from premature drug release. Premature release of a drug froma balloon is a major problem which has been addressed by a variety ofmethods. Some of them are mechanical, e.g. the use of protection tubes,sleeves, envelops. Examples are U.S. Pat. No. 5,370,614, U.S. Pat. No.6,306,166, and U.S. Pat. No. 6,616,650 disclosing various protectivesheaths which are retracted before the balloon is inflated, or U.S. Pat.No. 6,419,692 proposing a cover which bursts during balloon expansion. Adifferent approach is taken in U.S. Pat. No. 5,893,840 disclosingstructured balloon membranes with tiny cavities, WO 94/23787 withroughened balloon membranes to enhance the adherence of coating, or morerecently U.S. Pat. No. 7,108,684 proposing a pouch which protects thedrug-containing layer on the balloon and WO 2009/066330 disclosingmethods placing the drug selectively under the folds of a foldedballoon. Although efficacious these methods have the disadvantage ofincreasing the complexity and cost of production or make handling of thedevices more difficult or add to the diameter of the devices (which mustbe kept as small as possible to facilitate passage through stenoticlesions). In some embodiments the protective membranes or perforatedmembranes interfere with the scoring components of the balloons orprevent a homogeneous transfer of the drug to the tissue or even put thepatient at risk. None of these methods has been applied to scoring orcutting balloons and nothing is known about problems which will arisefrom the increasing complexity and mechanical problems arising from adisturbance of the protecting envelops by the scoring or cuttingstructures and vice-versa.

Other approaches use either physical or chemical methods to control therelease of drugs from a balloon surface, e.g. U.S. Pat. No. 5,304,121describes a hydrogel which releases the drug only after exposure to atriggering agent; U.S. Pat. No. 5,199,951 relies on thermal activation;according to U.S. Pat. No. 7,445,792 a lipophilic ^hydration inhibitor’protects water-soluble drugs from premature release; and according toU.S. Pat. No. 5,370,614 a viscous matrix protects the drug frompremature release, however, the viscous matrix must be protected by asheath during the passage to the stenotic vessel segment. None of themethods has been tested in practice and proven to fulfill therequirements for fast, reliable and complete drug transfer to the targettissue. None of the methods has been designed to be used with scoring orcutting balloons.

Numerous methods of sustained drug release are known and successfullyused in practice but are not applicable to medical devices which are incontact with the target tissue for only a few seconds or minutes.Sustained drug release is usually achieved by embedding the drug in apolymer which restricts the diffusion rate to the surface and in thisway controls the transfer into the adjacent tissue.

Therefore, a need remains for a method or formulation which protects thecoating from premature losses during production, handling, and on theway to the lesion and still allows the immediate and complete release ofthe active ingredient at a location and point in time determined by theuser. During the production process this problem is even more severe forscoring and cutting balloons because of the more complex structure ofthe product. Scoring and cutting balloons have merits in the treatmentof certain lesions, e.g. if the conventional smooth balloons tend todislocate during inflation or if a controlled and predetermined injuryof the vessel wall is preferred to an uncontrolled dissection duringballoon inflation. Nevertheless, the problem of renarrowing of thevessel lumen due to excessive neointimal proliferation as a reaction tothe unavoidable injury during dilatation is the same as withconventional balloon catheters.

An advantageous way to control adherence and release of a drug from amedical device, e.g., an angioplasty balloon, is the selection of asuitable formulation and coating which do not require mechanicalprotection, or additional physical or chemical interaction with thecoating except the usual operation of the device e.g. inflation of afolded balloon to induce the release of the drug. Although desirable andfrequently tried, the conflicting objectives of perfect adherence duringproduction and before use and immediate release at the site of actionmake it a difficult task. A large variety of patent applications vaguelydisclose measures, compositions and devices to solve this problem forconventional balloon catheters either by the selection of drugs, thechoice of specific coating processes or formulations containing variousadditives. Long lists of compounds have been copied from textbooks ofchemistry, pharmacology, or pharmacy but even with extensiveexperimentation disclosures are not sufficiently clear to allow a personfamiliar with the subject and skilled in the art to come to asatisfactory solution without an inventive step. Examples of prior artare US 2008/0118544 reciting an excessive number of substances andsubstance classes or U.S. Pat. No. 7,445,795 which discloses the use ofhydration inhibitors’ not applicable to the preferred class of verylipophilic drugs which require ^hydration enhancers’ as e.g. disclosedin WO 2004/028582. Although the hydrophilic additives (which may beregarded as ^hydration enhancer’) work quite well on certainconventional balloon membranes (Scheller B, Speck U, Abramjuk C,Bernhardt U, Bohm M, Nickenig G. Pa-clitaxel balloon coating—a novelmethod for prevention and therapy of restenosis. Circulation 2004; 110:810-814) the adherence to various modern conventional or scoring PTA orPTCA balloons is either too weak or too tight resulting in prematureloss of a major proportion of the drug or incomplete release at thetarget site. None of the known compositions has been tried on scoring orcutting balloon catheters.

Prior Art: Antioxidants.

In theory, antioxidants address an almost universal feature of diseasedtissue, namely the Reactive oxygen species’, and should have widespreadmedical applications. In practice, only very few controlled clinicaltrials have shown beneficial effects of antioxidants (Suzuki K.Antioxidants for therapeutic use: Why are only a few drugs in clinicaluse? Advanced Drug Delivery Reviews 2009; 61:287-289). Antioxidants arementioned as potentially useful drugs for the treatment of focalvascular disease such as stenosis, restenosis, atherosclerotic plaques,and vulnerable plaques in US 2009/0136560 with no additive, in U.S. Pat.No. 5,571,523 as agents inducing apoptosis in vascular smooth musclecells, in WO 2004/022124 either as active drugs or as ‘hydrationinhibitors’. In US 2008/0241215 probucol, a drug approved for thetreatment of hyperlipidemia, a known risk factor for atheriosclerosis,is proposed as the active ingredient in stent coating, either alone orcombined with rapamycin or another anti-restenotic agent in aslow-release formulation. None of the above-mentioned documents containsdata encouraging the use as additives to a lipophilic drug to delay therelease rate of the drug and no specific compositions are disclosedwhich address the above-mentioned problems of adhesion of a drug beforethe target lesion is reached and immediate release when required.

Small proportions of antioxidantsare commonly used to protect drugs ornutrients from decomposition by oxygen or oxidation, an applicationwhich has also been proposed for drugs coated on implantable medicaldevices such as stents (US 2007/0020380, US 2009/0246253) or ballooncatheters (US 2009/0246252, especially paragraph [105]). However,antioxidants are commonly used in proportions of less than 1% by weightin relation to 100% by weight of the drug. Normally it is intended touse as less antioxidant as possible, i.e., less than 0.1% by weight inrelation to 100% by weight of the drug (Voigt R. Lehrbuch derpharmazeutischen Technologie. 5. Edition, Verlag Chemie,Weinheim—Deer-field Beach, Fla.—Basel, 1984).

Present Invention.

The problem underlying the present invention was the provision of ascoring or cutting balloon catheter with an improved adherence of thedrug without negative effect on the release of the drug at the targetsite.

The problem was solved by a scoring or cutting balloon catheteraccording to claim 1. In other words, the problem was solved by ascoring or cutting balloon catheter carrying at least on a portion ofits surface at least one drug or drug preparation and at least onelipophilic antioxidant at a ratio of 3-100% by weight of the at leastone lipophilic antioxidant in relation to 100% by weight of the drug,wherein a combination of limus drugs with butylated hydroxytoluene asthe lipophilic antioxidant is excluded. Preferred embodiments aredisclosed in the dependant claims.

During testing of a large variety of coating methods, additives and drugcombinations the surprising discovery was made that certain lipophilicantioxidants added to even more lipophilic and less water soluble drugsin a defined mass ratio significantly increase the adherence of the drugto scoring and cutting balloons during handling and on the way to thetarget lesion even if the target lesion is located far away from thesite where the device first enters a blood-filled introductory sheath,guiding catheter or vessel containing rapidly flowing blood. This wasalso tested with scoring balloons. In spite of the additional mechanicalstress (as compared to conventional balloons) imposed on the coating duethe movement of the scoring wires surrounding the folded balloons theloss of the drug during the passage through a narrow hemostatic valveand a 3 curved guiding catheter was very low. Thus, at least onelipophilic antioxidant in an amount of 3-100% by weight is used as anadherence improver for drugs coated on a scoring or cutting ballooncatheter. The wording “at least one lipophilic antioxidant” means thatsingle antioxidants but also mixtures of different antioxidants areincluded.

Preferred examples of active drugs are inhibitors of cell proliferation,preferably taxanes such as paclitaxel, do-cetaxel and protaxel,immunosuppressants belonging to the class of substances binding to themammalian target of ra-pamycin (mTOR), i.e., mTOR inhibitors such assirolimus, everolimus, zotarolimus, biolimus and temsirolimus, mostpreferred is sirolimus, referred to as limus-drugs. Alternatively,specific inhibitors of neovascularization such as thalidomide, statinslike atorvastatin, cerivastatin, flu-vastatin or anti-inflammatory drugslike corticoids or even more preferred lipophilic derivatives ofcorticoids such as betamethasone diproprionate ordexamethasone-21-palmitate. Various drugs may be applied or combined ifdifferent pharmacological actions are required or efficacy or toleranceis to be improved. Thus, the wording “at least one drug or drugpreparation” means that single drugs but also mixtures of differentdrugs are included. Preferred drugs are either lipophilic (partitioncoefficient between n-butanol and water >10, or display very poor watersolubility (<1 mg/ml, 20° C.).

Preferred additives to the active drugs are lipophilic antioxidants,particularly preferred are antioxidants which are solid at temperaturesup to 40° C. Preferred are buty-lated hydroxytoluene, butylatedhydroxyanisole, nordihy-droguaiaretic acid, propyl gallate and ascorbylpalmitate. Probucol is not a preferred additive. The combination ofmTOR-binding limus-drugs with butylated hydroxytoluene is excluded asalready mentioned above. This applies to combinations of the single drugwith the single antioxidant as well as to combinations of butylatedhydroxytoluene with mixtures consisting of different Limus drugs.

Lipophilic antioxidant means that the partition coefficient of theantioxidant between n-butanol and water is >1, more preferred >10 andeven more preferred >100.

Preferably, the drug is more lipophilic than the antioxidant, i.e., thepartition coefficient between n-butanol and water of the drug is higherthan the partition coefficient between n-butanol and water of theantioxidant.

At the dose density used the chosen antioxidants do not display relevanttherapeutic or prophylactic effects in respect of the disease which istreated by the coated medical device nor is the relative amount of theantioxidant chosen to protect the drug from oxidative decomposition. Thedose density and the mass relation of the antioxidant to the drug aresolely optimized in respect of adherence of the drug to and release fromthe medical device surface. The antioxidant dose on the medical deviceis too low to provide the desired pharmacological effect, i.e., it isineffective on its own. The antioxidant on the medical device is notrequired to protect the active drug (e.g., the antiproliferative drug)from oxidative decomposition during production, sterilization andstorage; at least it is not required at the dose or concentrationapplied according to this invention. ‘Not required’ means that theactive drug is stable enough without the antioxidant or at anantioxidant dose or dose density or ratio to the active drug below thedose according to the present invention. ‘Sufficient stability’ meansthat less than 5% of the active drug is lost due to oxidativedecomposition between the coating of the device and the use in patientsone year after production if stored at ambient temperature (=drug ordrug preparation stable against oxidative decomposition).

The dose of the antioxidant on the surface of a medical device may bedefined in respect of the therapeutic drug. Preferred relationships(weight/weight) are 3-100% antioxidant of the weight of the drug. Forexample, if the dose density of the drug is 5 μg/mm² device surface, theamount of antioxidant is 0.15-5.0 μg/mm². Higher proportions of theantioxidant may be selected if either the drug is applied at a dosebelow 3 μg/mm² device surface or the adherence of the drug to the devicesurface is further improved. The antioxidant load of the device mayreach 10 μg/mm². A higher load is possible. Other preferred ranges forthe relationship of antioxidant to drug on a weight/weight basis are5-100%, more preferred 10-100%, and even more preferred 20-100% inrelation to 100% of the drug. The relationship may also be defined inrespect of moles: in a preferred embodiment the antioxidant is presentfrom 10 mole % relative to the drug to 200 mole %. Higher amounts of theantioxidant may be useful; they are only excluded if they display ontheir own significant pharmacological prophylactic or therapeuticeffects in respect of the disease to be treated application of the samecoating composition to more flexible modem balloon catheters resulted inproblems, i.e., larger premature loss of the drug. The coating ofscoring or cutting balloons with drugs in a reliable way with a dosewhich is sufficient to be efficacious imposes additional problemsbecause of the more complex structure of the device and the more complexproduction process.

If more than one drug is used the total weight of the drugs or the totalmoles of the drugs serve as basis for the calculation of the amount ofthe antioxidant. If more than one antioxidant is used the total weightof the antioxidants or the total moles of the antioxidants serve asbasis for the calculation of the amount of the antioxidants.

Polymer-free coating compositions are preferred. It is a specialadvantage of the present compositions that they do not require the useof polymers to prevent premature release of the drug.

Usually, drugs and mixtures of drugs with additives are coated onmedical devices as liquid formulations in volatile solvents. The choiceof solvent is important for the distribution of the drug on the device,especially if the device is coated at an advanced stage of production.An advanced stage of production of a scoring or cutting balloon mayinclude the scoring or cutting elements of the device, the structuresrequired to fix these elements and an already folded balloon. Thesolvents further determine the structure of the coating in dry state andthe adherence and release of the drug from the surface. Preferredorganic solvents are acetone, tetrahydrofuran, and various alcohols suchas methanol and ethanol. Usually, 1 to 30% (volume/volume) water isadded. The drug or drugs and the antioxidant may be applied at the sametime dissolved in the same solvent or mixture of solvents.Alternatively, they may be separately dissolved in the same or differentsolvents and sequentially applied. In a preferred embodiment, thescoring or cutting balloon catheter has been coated with at least onedrug and at least one antioxidant both together ore each separatelydissolved in tetrahydrofuran or a mixture of solvents containing morethan 25% (v/v) tetrahydrofuran. Another preferred embodiment is based ona scoring or cutting balloon catheter, which has been coated with atleast one drug and at least one antioxidant both together or eachseparately dissolved in acetone or a mixture of solvents containing morethan 25% (v/v) acetone. Coating with dry particles such as micro- ornanoparticles, crystals, capsules etc. or particles suspended in aliquid preparation is possible. Coating with particles may befacilitated by a roughened or sticky surface of the medical device.

A variety of coating procedures providing more or less uniform layers onmedical devices are known from the literature and are disclosed inpatent applications. These include simple dipping, spraying, and methodsproviding precise doses and homogeneous distributions (e.g., WO2009/018816). Coating may be applied stepwise, either as multiple layersof the same composition or as layers with different compositions e.g.the drug first and the antioxidant second or in the opposite order. Allthese methods may be applied to the formulations of the currentinvention. Furthermore, coated medical devices may be dried underdifferent conditions such as temperature, air flow, gas composition, andpressure at different stages of the production process. They may bestored in water-vapor-tight seals with a separately packed waterabsorbing-agent within the seal.

Subject of the current invention are scoring or cutting ballooncatheters, e.g., catheters for angioplasty or coronary angioplasty.Preferred are scoring or cutting balloon catheters for short-lasting useduring an interventional image guided therapy. Short lasting use meansthat the device is not implanted but eliminated from the body when theprocedure is finished, usually within less than 10 minutes, but neverlater than a few, preferably 5, hours after the end of the procedure.Catheters may contain balloon membranes made from various polymers andcopolymers, polyam-ides (nylon 12, pebax), polyethylenes, polyurethanes,various polyvinyls and the like. Independently of the type of material,the adherence and release properties of drugs are improved by theaddition of lipophilic antoxidants. Furthermore, catheters compriseelements which are aimed at scoring or cutting the surfaces in directcontact with the inflated balloons, e.g. wires with various profiles, orprotrusions of the balloon surface.

The scoring or cutting balloon catheter carries the at least one drug ordrug preparation and the at least one lipophilic antioxidant at least ona portion of its surface which is aimed at coming into close contactwith the tissue to be treated, e.g., the balloon at the distal portionof a catheter shaft. This means that at least 5%, preferably more than50%, most preferably more than 90% of the surface is coated. The balloonof a scoring or cutting balloon catheter has a central cylindrical partand two opposite conical ends. If less than 100% of the ballooncatheter's surface is coated, it is preferred that the cylindrical partis coated and that at least parts of or the complete conical ends remainuncoated.

Below, the invention is described by means of Examples.

Example 1

Balloons for percutaneous transluminal coronary angioplasty type A(AngioSculpt 3.5-20 mm, AngioScore, Inc., Fremont Calif., YSA werecoated either with paclitaxel alone or combined with iopromide(iodinated contrast agent according to WO 002/076509) or differentamounts of butylated hydroxy-toluene (BHT); solvent:acetone/ethanol/H₂O.Coated balloons were tested in respect of paclitaxel loss during thepassage through a hemostatic valve, Medtronic Launcher JL 3.5 6F guidingcatheter and one minute in stirred blood (37° C.). When admixed atsufficient concentration to the coating solution, BHT improved theadhesion of paclitaxel.

Loss on the way Catheter to the lesion Coating solution labeling % ofdose No additive 1 24 2 40 Iopromide as an additive; 3 49 ca. 0.5 mg/mgpaclitaxel 4 34 BHT 5% = 0.05 mg BHT/mg 5 15 paclitaxel 6 26 BHT 24% =0.24 mg BHT/ 7 10 mg paclitaxel 8 6

Example 2

Balloons for percutaneous transluminal coronary angioplasty type A werecoated either with paclitaxel alone or combined with iopromide(iodinated contrast agent according to WO 02/076509), see example 2, orbutylated hydroxytoluene (BHT) or nordihydroguaj aretic acid. Coatedballoons were tested in respect of paclitaxel loss during the passagethrough a hemostatic valve, a Medtronic Launcher JL 3.5 6F guidingcatheter and in stirred blood (37° C.) for one minute. When admixed atsufficient concentration to the coating solution, lipophilicantioxidants improve the adhesion of paclitaxel whereas the releaseduring balloon inflation in a coronary artery (determined in separateexperiments) was not impaired.

Loss on Residual the way to paclitaxel the lesion on balloons Coatingsolution Labeling % of dose % of dose No additive acetone/ethanol/H₂OControl 32 no data 1, 2 Iopromide as an additive; Control 42 ~10  ca.0.5 mg/mg paclitaxel; 3, 4 acetone/ethanol/H₂O BHT 24% = 0.24 mg BHT/mgA 15.3 ± 9.5  11 paclitaxel; acetone/ethanol/H₂O BHT 24% = 0.24 mgBHT/mg B 3.4 ± 4.8 13 paclitaxel; tetrahydrofuran/ ethanol/H₂ONordihydroguaiaretic acid C 4.2 ± 7.2 no data 35% = 0.35 mg/mgpaclitaxel; acetone/ethanol/H₂O

What is claimed is:
 1. A balloon catheter for angioplasty or coronaryangioplasty comprising: a shaft having a proximal portion and a distalportion; an inflatable balloon coupled to the distal portion of theshaft; a nonimplantable scoring structure surrounding the balloon,wherein the scoring structure is capable of scoring a luminal surface ofa blood vessel upon inflation of the inflatable balloon; wherein theballoon catheter carries on at least on a portion of its surface acoating composition comprising at least one drug and at least onelipophilic antioxidant that will protect the at least one drug frompremature loss during delivery to an angioplasty site and that is 3-100%by weight of the at least one drug, wherein the at least one drug isselected from the group consisting of a Limus drug, a cell proliferationinhibitor, and an inhibitor of neovascularization, wherein the at leastone lipophilic antioxidant is selected from the group consisting ofbutylated hydroxytoluene, butylated hydroxyanisole, nordihydroguaiareticacid, ascorbyl palmitate, and propyl gallate, and wherein a combinationof a Limus drug with butylated hydroxytoluene as the lipophilicantioxidant is excluded.
 2. The balloon catheter according to claim 1,wherein the scoring structure comprises one or more wires capable ofscoring the luminal surface upon inflation of the inflatable balloon. 3.The balloon catheter according to claim 1, wherein the at least one drugcomprises an oxidation-insensitive taxane selected from the groupconsisting of paclitaxel, protaxel and docetaxel.
 4. The ballooncatheter according to claim 3, wherein the at least one lipophilicantioxidant is nordihydroguaiaretic acid.
 5. The balloon catheteraccording to claim 3, wherein the oxidation-insensitive taxane isoxidation-insensitive paclitaxel.
 6. The balloon catheter according toclaim 5, wherein the at least one lipophilic antioxidant isnordihydroguaiaretic acid.
 7. The balloon catheter according to claim 1,wherein the at least one lipophilic antioxidant is nordihydroguaiareticacid.
 8. The balloon catheter according to claim 1, wherein the amountof the at least one lipophilic antioxidant protects the at least onedrug from premature loss during delivery to the angioplasty site.
 9. Theballoon catheter according to claim 1, wherein the at least oneantioxidant load is up to 10 μg/mm2 of coated catheter surface.
 10. Theballoon catheter according to claim 9, wherein the at least onelipophilic antioxidant is nordihydroguaiaretic acid.
 11. The ballooncatheter according to claim 1, wherein the at least one lipophilicantioxidant is contained at a ratio of 5-100% by weight, in relation to100% by weight of the at least one drug.
 12. The balloon catheteraccording to claim 11, wherein the at least one lipophilic antioxidantis nordihydroguaiaretic acid and the at least drug comprisesoxidation-insensitive paclitaxel.
 13. The balloon catheter according toclaim 1, wherein the at least one lipophilic antioxidant is contained ata ratio of 10-100% by weight, in relation to 100% by weight of the atleast one drug.
 14. The balloon catheter according to claim 13, whereinthe at least one lipophilic antioxidant is nordihydroguaiaretic acid andthe at least drug comprises oxidation-insensitive paclitaxel.
 15. Theballoon catheter according to claim 1, wherein the at least onelipophilic antioxidant is contained at a ratio of 20-100% by weight, inrelation to 100% by weight of the at least one drug.
 16. The ballooncatheter according to claim 15, wherein the at least one lipophilicantioxidant is nordihydroguaiaretic acid and the at least drug comprisesoxidation-insensitive paclitaxel.
 17. The balloon catheter according toclaim 1, wherein the at least one lipophilic antioxidant is contained ata ratio of 50-100% by weight, in relation to 100% by weight of the atleast one drug.
 18. The balloon catheter according to claim 17, whereinthe at least one lipophilic antioxidant is nordihydroguaiaretic acid andthe at least drug comprises oxidation-insensitive paclitaxel.
 19. Theballoon catheter according to claim 1, further comprising a coatingcomposition including the therapeutically effective amount of at leastone drug and an amount of at least one lipophilic antioxidant, whereinthe coating composition is polymer-free.
 20. The balloon catheteraccording to claim 19, wherein the at least one lipophilic antioxidantis nordihydroguaiaretic acid and the at least drug comprisesoxidation-insensitive paclitaxel.